We are studying the effect of the pineal gland hormone melatonin on the metabolism of human breast cancer cells. We have shown that melatonin rapidly enhances protein synthesis in human breast cancer cells. Pulse chase experiments of the melatonin-induced protein fraction demonstrates that this fraction translocates from the cytoplasm to the nucleus. Polyacrylamide electrophoresis of the cytoplasm of melatonin treated cells shows the presence of a 3,000 Dalton polypeptide in the melatonin but not vehicle treated cells. Translocation to the nucleus is associated with enhanced RNA synthesis. The RNA fraction which is enhanced has been shown to be ribosomal RNA. We are currently purifying and characterizing the melatonininduced polypeptide, and analyzing the effect of enhanced ribosomal RNA synthesis on growth and metabolism of these cells. We have also characterized the large molecular weight forms of the estrogen receptor in human breast cancer cells. We have shown that the ER is present as a 320 K and 600 K large molecular weight protein which is stabilized by protein inhibitors and not dissociated by high salt conditions. Studies are underway to further characterize these large molecular weight forms and to determine their significance in patients with breast cancer.